Biomedica : revista del Instituto Nacional de Salud最新文献

Chronic granulomatous disease is the inborn error of immunity with the highest frequency of invasive aspergillosis. In this context, invasive aspergillosis is frequent in adolescence, with rare cases before one year of age. We present a case of chronic granulomatous disease and invasive aspergillosis in a four-month-old infant.The patient was a male infant living in jail with his hypothyroid mother. He presented with a tumor in the left axillary region when he was four months old, and the chest X-ray suggested rib fractures. The patient was hospitalized on suspicion of child abuse. The chest computed tomography scan showed axillary abscess, rib osteolysis, pneumonia, and pulmonary nodules. He was treated with broad-spectrum antibiotics, and then he was discharged.Four months later, he was readmitted with fever and extension of the purulent abscess to the left scapular region; a computed tomography scan showed worsening images.Aspergillus fumigatus was isolated from the abscess pus, leading to an invasive aspergillosis diagnosis. The patient was treated with voriconazole for 28 days, andthen he was discharged. The chronic granulomatous disease was diagnosed by the dihydrorhodamine test. The mutated gene causing the inborn error of immunity was CYBB with the variant c.80_83del/Y; the mother was the carrier (c.80_83del/WT).At 12 months of age, the patient was readmitted for invasive aspergillosis, refractory to treatment, and died.This exceptional case teaches us how environmental conditions determine exposure to infectious agents in chronic granulomatous disease patients. Also, it illustrates that invasive aspergillosis can develope in infants with this pathology and should be treated aggressively.

Introduction: Immunodeficiencies are disturbances in the immune system that can affect cell function, quantity, or both. They can be either primary, associated with genetic defects, or secondary, linked to external factors such as hemato-oncological conditions. Secondary immunodeficiencies can lead to the initiation, reactivation, or acceleration of latent, residual, or active infections, which are the leading cause of mortality.

Objective: To elucidate the occurrence and clinical characteristics of hypogammaglobulinemia in pediatric oncology patients in a high-complexity hospital in Colombia between January 2020 and December 2022.

Materials and methods: We conducted an observational study with patients under 18 years old with a cancer diagnosis, serum immunoglobulins measurements at the time of the diagnosis, and later follow-up during treatment.

Results: We included 133 patients with a median age of eight years. Based on local guidelines of immunoglobulin levels for age, all patients had normal values at the time of cancer diagnosis. In the follow-up, the most significant reduction among all ages was for IgA and was related to infections and death.

Conclusions: Our findings highlight the importance of measuring immunoglobulin levels at the time of the cancer diagnosis, as hypogammaglobulinemia may be linked to a poorer prognosis. Early detection could potentially improve patient outcomes.

Introduction. The use of immunological tests before solid organ transplantation is essential to reduce the risk of rejection and post-transplant complications. Therefore, quality control systems in laboratories performing them are necessary for clinical practice. The Colombian Instituto Nacional de Salud implemented the external evaluation program of transplant immunogenetics laboratory performance in 2014.Objective. To evaluate the performance of the laboratories that carried out five of the immunological tests for transplants in Colombia between 2014 and 2023, according to information from the external evaluation program of transplant immunogenetics laboratory performance.Materials and methods. We conducted a study of laboratory performance considering five immunological tests for transplantation: HLA, qualitative and quantitative PRA (Panel Reactive Antibodies), isolated antigen, and cross-matching tests. We collected data from reports of each laboratory. Based on the comparisons between laboratories, their performance was rated as “good”, “acceptable”, or “unacceptable” for each test. We calculated proportions and an analysis of predicted values with a 95% confidence interval.Results. The number of participating laboratories varied between 5 and 12, depending on the test. The proportion of laboratories with “good” performance was lower in the first year. The best performance was for qualitative PRA, rated as good in all the laboratories for eight years. In HLA (2014), qualitative PRA (2017 and 2019), crossmatch tests (2019), and single antigen (2017 and 2019) tests, the laboratories had a lower percentage of “good” performance than expected.Conclusion. “Good” performance was observed in all the laboratories in each test during the last three years, except for HLA and quantitative PRA.

In this manuscript, we carried out an exhaustive analysis of the global recommendations for immunization in inborn errors of immunity patients. We examined the mechanisms of action and types of vaccines, and we described the vaccines included in the Colombian immunization program together with the specific guidelines for immunization in patients with the most frequent inborn errors of immunity in Colombia.These recommendations were adjusted according to the severity and subclassifications of each immunodeficiency, considering variations in the immune response to offer evidencebased recommendations for vaccination in children with these conditions. We included the most common inborn errors of immunity worldwide and considered the vaccines included in the Colombian immunization program to avoid delays in vaccination schedules.This work was achieved through a narrative, non-systematic review of articles indexed in Spanish and English, using MeSH terms such as: “inborn errors of immunity”, “primary immunodeficiencies”, “vaccination in inborn errors of immunity, “types of vaccines”, “mechanism of action of vaccines”, and “live vaccines in inborn errors of immunity”.We used search engines such as: PubMed, Medline, ScienceDirect, and websites of recognized institutions such as the Centers for Disease Control and Prevention (CDC).

Inborn errors of immunity are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Some autoimmune diseases, such as autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases, are increasingly recognized as phenotypes of inborn errors of immunity. The objective of this article was to identify red flags or clinical/laboratory markers to suspect inborn errors of immunity in patients with autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases through a systematic literature review. The study followed the systematic reviews and meta-analysis guidelines (PRISMA). After selection, we included 36 articles, and their methodological quality was verified using the Joanna Briggs Institute tools for individual risk of bias analysis. The principal red flags in autoimmune cytopenias are chronic, recurrent, and refractory cytopenias, recurrent infection, severe infectious complications associated with immunosuppressive treatment, and chronic lymphoproliferation. In systemic lupus erythematosus, red flags include age of onset before five years, severe organ involvement, chilblain lesions, and chronic lymphoproliferation. For inflammatory bowel diseases, red flags are an age of onset before two years, resistance to conventional therapies, atypical endoscopic or histologic findings, and consanguineous parents. Autoimmune diseases may be the primary manifestation of inborn errors of immunity in pediatric and adult patients. An early diagnosis of a monogenic disorder allows for the tailoring of effective treatment plans, providing prognostic information to families, and offering genetic counseling.

Introduction: Common variable immunodeficiency is a diagnosis of exclusion in immunodeficient patients with increased susceptibility to infections, hypogammaglobulinemia, deficient response to vaccination, or low percentages of switched memory B cells. In low- and middle-income countries, the elucidation and study of molecular defects in these patients may take decades.

Objective: To elucidate the genetic defect conferring impaired immunity in a patient diagnosed with common variable immunodeficiency.

Materials and methods: The clinical phenotype was extracted from the clinical records. NKG2D expression in natural killer cells was evaluated by flow cytometry. The whole exome sequencing was performed in the patient and his parents. Sanger sequencing confirmed the pathogenic variant.

Results: The patient suffered from upper respiratory and urinary tract infections, autoimmune hemolytic anemia, and hepatopathy. NKG2D was decreased in the different blood subpopulations of natural killer cells. Serologic and viral load studies for Epstein-Barr virus were positive, but no B-cell malignancies have been documented. The patient presented a nonsense variant in the exon 3 of the MAGT1 gen (c.409C>T, rs387906724) in the X chromosome, resulting in an amino acid substitution of arginine for a stop codon in the position 137 of the protein (R137X). The mother also carried the pathogenic variant in a heterozygous state.

Conclusions: We report the clinical case of the first Colombian male patient with a pathogenic variant in MAGT1 associated with XMEN disease. Genetic counseling and followup are recommended for families with similar cases to allow prompt detection of new cases.

Introduction: Chronic granulomatous disease is a defect in phagocytosis due to deficiency of gp91phox, p22phox, p47phox, p40phox, and p67phox (classic form of the disease). Recently, EROS and p40phox deficiency were described as responsible for the non-classical form of the disease. The 1,2,3-dihydrorhodamine oxidation technique, with phorbol-12-myristate-13-acetate as a stimulus, is performed to diagnose the classic chronic granulomatous disease. However, oxidation mediated by EROS and p40phox requires stimuli such as zymosan, Escherichia coli, or Staphylococcus aureus.

Objective: To optimize the 1,2,3-dihydrorhodamine technique using zymosan to assess neutrophil respiratory burst and detect the non-classical chronic granulomatous disease.

Materials and method: Blood was obtained from five healthy subjects after the signature of the informed consent. The 1,2,3-dihydrorhodamine technique was performed with phorbol-12-myristate-13-acetate as control and different quantities of opsonized zymosan (150, 100, 50, 20, and 10 μg). We obtained through flow cytometry the mean fluorescence intensity of rhodamine 1,2,3 oxidated in the neutrophil population and calculated the oxidation index. The Kolmogorov-Smirnov test, ANOVA, and Tukey’s post-hoc analysis were used. We considered a p value ≤ 0.05 as statistically significant.

Results: The phorbol-12-myristate-13-acetate increased the rhodamine 1,2,3 mean fluorescence intensity in healthy subjects. Among the different zymosan conditions tested, we selected 50 μg as the optimal and reproducible amount in all controls according to the statistical analysis and cytometric findings.

Conclusions: We present the optimization of the 1,2,3-dihydrorhodamine technique using zymosan. We propose its implementation in clinical diagnostic laboratories to expand the diagnosis of chronic granulomatous disease.

Autoimmune responses are characterized by the development of antibodies and the activation of T lymphocytes against self-antigens. This leads to an effector immune response against tissues expressing antigens, which are later recognized by the host immune system. Host antigens attacked by antibodies are called "autoantigens" and are of different kinds, including receptors, enzymes, and channel proteins. The autoimmune response is potentiated by cytokines that mediate the activation of Th1, Th2, or Th17 lymphocytes. The released cytokines can also be recognized as autoantigens, meaning they can be targets of the autoimmune response. The effects of autoimmunity on cytokines or their receptors are diverse, and the mechanisms of this type of autoimmune response are discussed in this review.

Introduction: Inborn errors of immunity is a diverse group of rare diseases caused by over 400 genetic mutations affecting the immune system and increasing infection susceptibility, autoimmunity, and malignancy. Hematopoietic stem cell transplantation offers a curative option for some inborn errors of immunity, with haploidentical donors providing a viable alternative when identical donors are unavailable.

Objective: To determine survival, usefulness of weekly chimerism monitoring, immune reconstitution, and complications in patients with inborn errors of immunity who underwent haploidentical hematopoietic stem cell transplantation at a reference center in Colombia.

Materials and methods: We conducted a retrospective and observational study of a case series of pediatric patients who underwent haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and follow-up with weekly chimerism. Survival analysis was performed using the Kaplan-Meier method.

Results: Sixteen patients with haploidentical familial donor transplantation were included. The most frequent diagnosis was severe combined immunodeficiency (n=5). Eleven out of seventeen patients received a non-myeloablative conditioning regimen. Twelve out of sixteen patients developed acute graft-versus-host disease. Out of these, 3 corresponded to grades III-IV. Post-transplant infections affected 14 of the subjects, predominating bacterial agents. Median T-cell chimerism was greater than 80% during the follow-up. Reconstitution of B and T lymphocytes was achieved in more than 80%. Overall survival at five years was 81%. Survival at 100 days was 94%.

Conclusion: Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide is a viable alternative for inborn errors of immunity when an identical donor is unavailable. Serial chimerism monitoring is useful for graft follow-up.